In this study, we examine the effect of chemokine (C-C motif) ligand 5 (CCL5)/Regulated on Activation Normal T cell Expressed and Secreted (RANTES), a pro-inflammatory cytokine on osteogenic differentiation of human mesenchymal stem cells (hMSCs). We found CCL5 expression was increased during osteogenic differentiation of hMSCs and CCL5 expression is dependent on the presence of dexamethasone. Knocking down endogenous CCL5 expression blocked osteogenesis, as revealed by decreasing alkaline phosphatase (ALP) activity and a reduction in the expression levels of ALP, bone sialoprotein (BSP), and osteopontin (OPN). Of note, the overexpression of CCL5 was sufficient to increase ALP expression and activity. Moreover, the down-regulation of chemokine (C-C motif) receptor 1 (CCR1), one of the CCL5 receptors, significantly decreased the osteogenesis of hMSCs. Interestingly, the down-regulation of CCR1, but not CCL5, was sufficient to affect the cell numbers during the process of osteogenesis. Our findings reveal that both CCL5 and CCR1 are required for osteogenesis of human MSCs, CCL5 is sufficient for the osteogenesis, and provide a novel link between dexamethasone and CCL5 in human osteogenesis.
Hypoxia may play an important role in the pathogenesis of systemic sclerosis (SSc). Carbonic anhydrase IX (CA IX) is one of the hypoxia markers and its extracellular domain can be released into the serum. However, the clinical significance of serum CA IX levels in SSc is still unknown. The aim of this study is to evaluate the possibility that serum CA IX levels can be a specific disease marker of SSc. Serum samples were obtained from SSc patients and healthy controls. Patients diagnosed as scleroderma spectrum disorder (SSD), who did not fulfill the ACR criteria of SSc but were thought that they might develop SSc in the future, were also included in this study. Serum CA IX levels were measured with specific enzyme-linked immunosorbent assays. SSD patients had significantly lower CA IX levels than diffuse cutaneous SSc (dcSSc), limited cuntaneous SSc (lcSSc) and healthy control groups. Also, we found a significant decrease in the values in dcSSc patients compared to those of lcSSc patients. Serum levels of CA IX may be useful for the differentiation of lcSSc from SSD. Decreased serum CA IX levels in spite of the presence of hypoxia in SSc may indicate an impaired response to hypoxia, which leads to the persistent hypoxic condition. Our results suggest that the abnormal response to hypoxia may already exist in SSD patients, and may be involved in its pathogenesis.
It is of importance to determine whether antipsychotic drugs currently prescribed for schizophrenia exert D-amino acid oxidase (DAO)-inhibitory effects. We first investigated whether human (h)DAO can metabolize D-kynurenine (D-KYN) to produce the fluorescent compound kynurenic acid (KYNA) by using high-performance liquid chromatography with mass spectrometry, and fluorescence spectrometry. After confirmation of KYNA production from D-KYN by hDAO, 8 first- and second-generation antipsychotic drugs, and 6 drugs often prescribed concomitantly, were assayed for hDAO-inhibitory effects by using in vitro fluorometric methods with D-KYN as the substrate. DAO inhibitors 3-methylpyrazole-5-carboxylic acid and 4H-thieno[3,2-b]pyrrole-5-carboxylic acid inhibited KYNA production in a dose-dependent manner. Similarly, the second-generation antipsychotics blonanserin and risperidone were found to possess relatively strong hDAO-inhibitory effects in vitro (5.29 ± 0.47 μM and 4.70 ± 0.17 μM, respectively). With regard to blonanserin and risperidone, DAO-inhibitory effects should be taken into consideration in the context of their in vivo pharmacotherapeutic efficacy.
The effects of anesthesia with sevoflurane and with propofol on glucose utilization in rats were investigated. Sevoflurane significantly impairs glucose utilization whereas propofol does not. Both insulin secretion and sensitivity affect glucose utilization. Propofol is hydrophobic, and anesthesia with this agent is always accompanied by an acute lipid load, which can exaggerate insulin resistance. The role of the acute lipid load in the effects of anesthesia with sevoflurane and propofol on glucose utilization in fasted rats was investigated. Rats were allocated to groups anesthetized with sevoflurane and infused with physiological saline (group S) or 10% w/v lipid (group SL), or those anesthetized with propofol (group P). Intravenous glucose tolerance tests and insulin tolerance tests were then performed to measure glucose utilization, and blood glucose, plasma insulin, and plasma TNF-α levels were measured. In the intravenous glucose tolerance test, groups SL and P showed significantly higher plasma insulin levels than group S, and group P showed significantly higher plasma insulin levels than group SL. In the insulin tolerance test, groups SL and P showed insulin resistance compared to group S, but no significant difference was observed between groups SL and P. In summary, propofol anesthesia enhances insulin secretion and concomitantly exaggerates insulin resistance, compared with sevoflurane anesthesia. Propofol appears to be the main cause of hyperinsulinemia, and the acute lipid load exaggerates insulin resistance.
This study sought to evaluate the performance of the T-SPOT.TB assay for the diagnosis of active tuberculosis (TB) in human immunodeficiency virus (HIV) infected patients. One hundred confirmed HIV-infected patients with active TB and known T-SPOT.TB and CD4+ T-cell counts were enrolled in this clinical retrospective study. We found that patients with lower CD4+ T-cell counts (11-50 cells/μL) had the lowest T-SPOT.TB positive rates (50%), and patients with higher CD4+ T-cell counts (50-100 cells/μL) had the highest T-SPOT.TB positive rates (75%). However, there were no significant differences between the T-SPOT.TB positive rates of patients with different CD4+ T-cell counts (< 10, 11-50, 51-100 and > 100 cells/μL) (χ2 = 3.7747, p = 0.287). The patients with positive TB culture results had significantly higher T-SPOT.TB positive rates (78.9%) than patients that were culture-negative (44.3%) (χ2 = 12.8303, p < 0.001). Other variables, including gender, age, TB disease classification, HIV RNA level, and highly reactive antiretroviral therapy (HAART), had no significant effects on T-SPOT.TB positive rates. The number of spot-forming cells (SFCs) reactive with ESAT-6, CFP-10 and ESAT-6/CFP-10-specific T cells detected by T-SPOT.TB were positively is strongly related to the degree of immunodeficiency, while the T-SPOT.TB positive rates are less dependent on the level of CD4+ T-cell depletion in HIV infection and active TB.
Fibrin sealant (FS) and tranexamic acid (TXA) have been used in total knee arthroplasty (TKA) to minimize perioperative blood loss. The efficacy of FS has been debated, and few studies have looked into the effects of FS and TXA on perioperative coagulability. The current study retrospectively reviewed 100 cases of unilateral primary TKA. Twenty-five cases served as blank controls, FS was used without TXA in 23, TXA was used without FS in 20, and both FS and TXA (FS + TXA) were used in 32. FS was sprayed before wound closure whereas 1 g of TXA was intravenously administered before incision and 1 g was administered 15 min before tourniquet release. Hematocrit and hemoglobin levels and thromboelastography (TEG) parameters were assessed pre-operatively and on day 1, 4, and 9 post-operatively. Blood transfusions were noted and the incidence of symptomatic DVT/PE was determined. Hematocrit and hemoglobin levels were significantly higher in the TXA and FS + TXA groups compared to the control and FS groups on day 1, 4, and 9 post-operatively. Hematocrit and hemoglobin levels in the control group were similar to those in the FS group and hematocrit and hemoglobin levels in the TXA group were similar to those in the FS + TXA group. TEG parameters (R, K, α, MA, and CI) remained within normal ranges. Mean CI was less than +3 in all four groups, suggesting that hypercoagulation was not promoted. One patient in the FS group received an allogeneic transfusion. Incidence of symptomatic DVT/PE was not noted. Intravenous TXA significantly reduced perioperative blood loss in patients undergoing a TKA but FS did not. Administration of FS in addition to TXA was not superior to TXA alone. FS and/or TXA did not increase the risk of hypercoagulation according to TEG parameters. Intravenous administration of 1 g of TXA pre-operatively and administration of 1 g before tourniquet release is an effective and safe method of reducing blood loss in TKA.
Oxidative stress plays a major pathological role in pregnancy-related complications. Although oxidative stress is induced by exogenous toxins in association with a poor lifestyle in normal subjects, there is little information on the factors altering oxidative stress and antioxidant levels during pregnancy. The purpose of this study was to determine the relationship between lifestyle factors and oxidative stress/antioxidant levels during each trimester and 1-month postpartum. This prospective cohort study followed 54 healthy women through pregnancy; first, second, and third trimester and 1-month postpartum. Participants were administered a questionnaire on characteristics and lifestyle factors. Morning blood and urine samples were obtained to measure urinary biopyrrins and serum coenzyme Q10 (CoQ10) levels. The levels of urinary biopyrrins and serum CoQ10 increased significantly throughout pregnancy, with peak values registered during the third trimester. Higher biopyrrin levels were significantly associated with non-consumption of morning meal during the first trimester, smoking during the third trimester and 1-month postpartum, alcohol consumption during the third trimester, high food-based polyunsaturated fatty acid intake during the third trimester, and poor mental health scores during the first and third trimesters. Higher CoQ10 levels were significantly associated with no smoking during pregnancy and at 1-month postpartum, and with a high frequency of exercise during the third trimester and 1-month postpartum. Thus, pregnancy represents a state of oxidative stress, which can be counterbalanced by increased levels of antioxidants, such as CoQ10. We speculate that certain lifestyle choices such as avoiding smoking can reduce oxidative stress and increase antioxidant levels during pregnancy.
Primary hepatic mucosa-associated lymphoid tissue (MALT) lymphoma has a low incidence and is a rare subtype of hepatic malignant lymphoma. Described here is a rare case of primary hepatic MALT lymphoma and hepatic hemangioma with chronic HBV infection as an underlying condition. Possible treatment modalities, which should be selected in accordance with tumor size, tumor location, tumor number, and underlying liver disease, are discussed in conjunction with a review of the literature. In addition, the potential use of hepatic resection, radio frequency ablation (RFA), or radiotherapy followed by chemotherapy via the R-CHOP regimen is also discussed.
In more than 20 years of medical practice, a surprising phenomenon has often occurred: some patients with acquired immunodeficiency syndrome (AIDS) decide not to go to the hospital and they do not let others know that they are suffering from the disease unless they believe that they are dieing. Zhang Shan (a pseudonym) is one such patient with human immunodeficiency virus (HIV)/AIDS who was reluctant to receive antiviral therapy as soon as possible, and this paper shares Zhang's story as he related it. Clearly, there are numerous views as to why patients in China behave as Zhang did. Presented here are several reasons, including society, history, morality and ideology, family, and education. Although all of these reasons do play a role, the patient’s mindset and behavior is the most significant reason for a patient’s reluctance to seek treatment or disclose his/her status. If the individual patient’s mindset and behavior are not dealt with effectively, then HIV/AIDS can continue to spread and threaten additional lives and even the fabric of society. This paper analyzes the reasons why patients are hesitant to receive antiviral therapy, but this paper also suggests steps healthcare personnel can take to encourage patients to seek treatment. Such steps can save the lives of current patients with HIV/AIDS. In addition, sound public health measures and a rational approach to treatment are important to helping potential patients with HIV/AIDS.